Abnormalities Of Peripheral Blood Lymphocyte Subsets In Rheumatoid Arthritis Patients With Osteoporosis And Its Clinical Significance

Objective:To investigate the status of peripheral blood lymphocyte subsets in rheumatoid arthritis patients with osteoporosis and explore its clinical significance.Methods:A total of 734 patients with RA and 81 healthy controls(HC)were enrolled in this study.All peripheral lymphocyte subsets of these participants were assessed by flow cytometry combined with standard absolute counting beads.Patients were divided into RA-non-OP group and RA-OP group according to their BMD of lumbar or bilateral hip and the history of fragility fracture for further comparation of general clinical character.At the same time the difference of peripheral blood lymphocyte subsets among HC,RA-non-OP and RA-OP participatients were compared.Further,the correlation between BMD and the lymphocyte subsets in RA-OP patients were also analyzed.Results:The incidence of OP in RA patients was 24.93%,of which 12.57% had old fractures.Interestingly,patients with OP are more obvious in female(P=0.021),especially with older age(61.85±10.36 vs.56.63±12.01,P<0.001),a longer disease duration(7.17±5.82 vs.5.28±6.33,P=0.001)and higher disease activity measures such as swollen joint counts(5.24±6.37 vs.4.57±6.22,P=0.004),tender joint counts(8.97±8.36 vs.8.36±8.04,P=0.043),ESR(64.92±35.58 vs.52.25±34.65,P<0.001),CRP(38.38±50.69 vs.33.97±42.67,P=0.014)and DAS-28 score(5.19±1.23 vs.4.79±1.32,P<0.001).There was no statistical difference in the laboratory indexes of blood parameters and hepatorenal and kidney function between RA patients with OP and without OP(P>0.05).Compared with HC,the level of B cells in RA-non-OP group was slightly decreased,whereas Th17 mildly increased(P>0.05).There were distinct increases in the Th2 cells(8.40±4.55 vs.11.53±8.99;1.29±0.75 vs.1.78±1.25,P<0.01)and the ratio of Th17/Treg(0.19±0.11 vs.0.33±0.44,P<0.01).The absolute number and the proportion of Treg cells(35.92±13.03 vs.31.20±19.22;5.33±1.41 vs.4.69±2.08,P<0.05)and the ratio of Th1/Th2(17.52±24.73 vs.10.03±9.18,P<0.05)were lower.The decrease of B cells was more obvious in patients with OP(201.99±83.28 vs.160.31±108.70,P<0.05).There were also increase in Th17 cells(6.41±3.52 vs.8.35±6.99;0.97±0.54 vs.1.35±1.21,P<0.01)and the ratio of Th17/Treg(0.19±0.11 vs.0.41±0.58,P<0.01).However,Treg cells decreased distinctly(35.92±13.03 vs.26.73±16.37;5.33±1.41 vs.4.24±1.82,P<0.001).Compared with RA-non-OP group,the level of B(186.71±111.55 vs.160.31±108.70;11.56±5.34 vs.10.35±5.62,P<0.01)and Treg(31.32±19.22 vs.26.73±16.37;4.69±2.08 vs.4.24±1.82,P<0.01)cells in RA-OP group were lower.There were significant increases in Th17 cells(7.36±5.36 vs.8.35±6.99;1.17±0.87 vs.1.35±1.21,P<0.05)and the ratio of Th17/Treg(0.33±0.44 vs.0.41±0.58,P< 0.05).The BMD of lumbar spine in RA-OP patients was positively correlated with the level of B(r=0.290 、0.315,P< 0.05)and Treg cells(r=0.318 、0.248,P<0.05),and negatively with Th17 cells(r=-0.254 、-0.265,P<0.05)and Th17/Treg ratio(r=-0.242,P<0.05).Similarly,the BMD of the either hip in RA-OP patients was positively correlated with the level of B(r=0.238、0.256,P< 0.05)and Treg cells(r=0.259、0.255,P<0.05),and negatively with Th17 cells(r=-0.248 、-0.283,P<0.05)and Th17/Treg ratio(r=-0.216,P<0.05).Conclusion:Gender,age,disease course and disease activities may play a role in the development of OP in patients with RA,which could be used as a reference index for the occurrence risk of OP.The insufficiency of B cells and the immune disorder such as Th17/Treg imbalance might contribute to OP in RA patients.It is important to pay more attention to the immune microenvironment.Immune regulation intervene should be considered at the early stage of RA disease to prevent the occurrence of OP.